Dynamic mucus secretion in ventral surfaces of toe pads of the tree frog (Dryophytes japonica).

The tree frog is a prominent amphibian among terrestrial vertebrates known for its ability to adhere to various surfaces through the capillary forces of water in the microchannels between micropillars on its disc-shaped toe pads, a phenomenon known as wet adhesion. However, the secretion pattern of mucus on the attachment surface of living tree frog toe pads and the distribution of active mucus pores (AMPs) have not yet been fully elucidated. In this study, we utilized synchrotron X-ray micro-computed tomography and interference reflection microscopy to obtain the spatial distribution of the entire population of ventral mucus glands on the toe pads of living tree frogs and the real-time mucus secretion patterns from the ventral mucus pores on the contact surface under different environmental conditions. We observed that the number and secretion frequency of AMPs on the toe pad are regulated according to environmental conditions. Such dynamic mucus secretion on the tree frog's toe pad could contribute to the understanding of capillary force regulation for wet adhesion and the development of adhesive surfaces by mimicking the mucus-secreting toe pad.

Methanol extract of Elsholtzia fruticosa promotes 3T3-L1 preadipocyte differentiation.

Elsholtzia fruticosa (EF) is present in tropical regions throughout South Asian countries as well as the Himalayas. Although it has been used as a traditional medicine to treat digestive, respiratory, and inflammatory issues, its effect on preadipocyte differentiation is unknown. In this study, we examined the effects of a methanol extract prepared from EF on the differentiation of 3T3-L1 preadipocytes. Cell differentiation was assessed by microscopic observation and oil-red O staining. The expression of adipogenic and lipogenic genes, including PPARγ and C/EBPα, was measured by western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR), to provide insight into adipogenesis and lipogenesis mechanisms. The results indicated that EF promotes the differentiation of 3T3-L1 preadipocytes, with elevated lipid accumulation occurring in a concentration-dependent manner without apparent cytotoxicity. EF enhances the expression of adipogenic and lipogenic genes, including PPARγ, FABP4, adiponectin, and FAS, at the mRNA and protein levels. The effect of EF was more pronounced during the early and middle stages of 3T3-L1 cell differentiation. Treatment with EF decreased C/EBP homologous protein (CHOP) mRNA and protein levels, while increasing C/EBPα and PPARγ expression. Treatment with EF resulted in the upregulation of cyclin E and CDK2 gene expression within 24 h, followed by a decrease at 48 h, demonstrating the early-stage impact of EF. A concomitant increase in cyclin-D1 levels was observed compared with untreated cells, indicating that EF modulates lipogenic and adipogenic genes through intricate mechanisms involving CHOP and cell cycle pathways. In summary, EF induces the differentiation of 3T3-L1 preadipocytes by increasing the expression of adipogenic and lipogenic genes, possibly through CHOP and cell cycle-dependent mechanisms.

Stellera chamaejasme L. extract inhibits adipocyte differentiation through activation of the extracellular signal-regulated kinase pathway.

Stellera chamaejasme L. (SCL) is a perennial herb with demonstrated bioactivities against inflammation and metabolic dysfunction. Adipocyte differentiation is a critical regulator of metabolic homeostasis and a promising target for the treatment of metabolic diseases, so we examined the effects of SCL on adipogenesis. A methanol extract of SCL dose-dependently suppressed intracellular lipid accumulation in adipocyte precursors cultured under differentiation induction conditions and reduced expression of the adipogenic transcription factors PPARγ and C/EBPα as well as the downstream lipogenic genes fatty acid binding protein 4, adiponectin, fatty acid synthase, and stearoyl-CoA desaturase. The extract also promoted precursor cell proliferation and altered expression of the cell cycle regulators cyclin-dependent kinase 4, cyclin E, and cyclin D1. In addition, SCL extract stimulated extracellular signal-regulated kinase (ERK) phosphorylation, while pharmacological inhibition of ERK effectively blocked the inhibitory effects of SCL extract on preadipocyte differentiation. These results suggest that SCL extract contains bioactive compounds that can suppress adipogenesis through modulation of the ERK pathway.

Proinsulin C-peptide inhibits high glucose-induced migration and invasion of ovarian cancer cells.

Proinsulin C-peptide, a biologically active polypeptide released from pancreatic ß-cells, is known to prevent hyperglycemia-induced microvascular leakage; however, the role of C-peptide in migration and invasion of cancer cells is unknown. Here, we investigated high glucose-induced migration and invasion of ovarian cancer cells and the inhibitory effects of human C-peptide on metastatic cellular responses. In SKOV3 human ovarian cancer cells, high glucose conditions activated a vicious cycle of reactive oxygen species (ROS) generation and transglutaminase 2 (TGase2) activation through elevation of intracellular Ca2+ levels. TGase2 played a critical role in high glucose-induced ovarian cancer cell migration and invasion through ß-catenin disassembly. Human C-peptide inhibited high glucose-induced disassembly of adherens junctions and ovarian cancer cell migration and invasion through inhibition of ROS generation and TGase2 activation. The preventive effect of C-peptide on high glucose-induced ovarian cancer cell migration and invasion was further demonstrated in ID8 murine ovarian cancer cells. Our findings suggest that high glucose conditions induce the migration and invasion of ovarian cancer cells, and human C-peptide inhibits these metastatic responses by preventing ROS generation, TGase2 activation, and subsequent disassembly of adherens junctions.

Establishment of an LC-MS/MS method for quantification of lifitegrast in rabbit plasma and ocular tissues and its application to pharmacokinetic study.

Lifitegrast, a lymphocyte function-associated antigen 1 antagonist, was approved by the FDA for the treatment of dry eye disease. Cornea and conjunctiva have been reported to be the sites of action of lifitegrast. To investigate the pharmacokinetics of lifitegrast, a sensitive analytical method for the determination of lifitegrast in various biological matrices such as plasma and ocular tissues is required. However, only limited information about the analytical method for lifitegrast in biological samples is available. In the present study, we aimed to develop a new liquid chromatography-tandem mass spectrometry method for the determination of lifitegrast in rabbit plasma, cornea, conjunctiva, and sclera. Lifitegrast-d6 was used as an internal standard (IS). To prepare the biological samples, protein precipitation using acetonitrile was utilized. Analytes were separated from endogenous interferences on an Atlantis dC18 (5 µm, 2.1 × 150 mm), and a mixture of 0.1 % formic acid and acetonitrile was used as the mobile phase. The mass transition of precursor to product ion was monitored at 615.2 â†’ 145.0 for lifitegrast and 621.2 â†’ 145.1 for IS. The calibration curves were linear over the concentration range from 2 to 500 ng/mL for plasma and 5 to 500 ng/mL in ocular tissue homogenates. Intra- and inter-day accuracy ranged from 95.76 to 106.80 % in the plasma and 94.42 to 112.80 % in the ocular tissues. Precision was within 8.56 % in the plasma and 9.72 % in the ocular tissues. The short-term, long-term, auto-sampler, and freeze-thaw stabilities of lifitegrast were validated. The developed method was applied to a pharmacokinetic study of lifitegrast in rabbits. Following ophthalmic administration, only 3.26 % of administered lifitegrast was absorbed into the systemic circulation. Peak tissue concentrations were observed at 0.5 h after dosing, and topically administered lifitegrast was mainly distributed in the cornea and conjunctiva. The finding of this study is expected to be used in further pharmacokinetic studies and formulation development.

Therapeutic effect of ultra-long-lasting human C-peptide delivery against hyperglycemia-induced neovascularization in diabetic retinopathy.

Rationale: Neovascularization is a hallmark of the late stages of diabetic retinopathy (DR) leading to blindness. The current anti-DR drugs have clinical disadvantages including short circulation half-lives and the need for frequent intraocular administration. New therapies with long-lasting drug release and minimal side effects are therefore needed. We explored a novel function and mechanism of a proinsulin C-peptide molecule with ultra-long-lasting delivery characteristics for the prevention of retinal neovascularization in proliferative diabetic retinopathy (PDR). Methods: We developed a strategy for ultra-long intraocular delivery of human C-peptide using an intravitreal depot of K9-C-peptide, a human C-peptide conjugated to a thermosensitive biopolymer, and investigated its inhibitory effect on hyperglycemia-induced retinal neovascularization using human retinal endothelial cells (HRECs) and PDR mice. Results: In HRECs, high glucose conditions induced oxidative stress and microvascular permeability, and K9-C-peptide suppressed those effects similarly to unconjugated human C-peptide. A single intravitreal injection of K9-C-peptide in mice resulted in the slow release of human C-peptide that maintained physiological levels of C-peptide in the intraocular space for at least 56 days without inducing retinal cytotoxicity. In PDR mice, intraocular K9-C-peptide attenuated diabetic retinal neovascularization by normalizing hyperglycemia-induced oxidative stress, vascular leakage, and inflammation and restoring blood-retinal barrier function and the balance between pro- and anti-angiogenic factors. Conclusions: K9-C-peptide provides ultra-long-lasting intraocular delivery of human C-peptide as an anti-angiogenic agent to attenuate retinal neovascularization in PDR.

Development of an LC-MS/MS Assay and Toxicokinetic Characterization of Hexamethylenetetramine in Rats.

Hexamethylenetetramine, an aldehyde-releasing agent, is used as a preservative in various food, cosmetics, and medical treatments, such as a treatment for urinary tract infections. It has been reported to be allergenic on contact with the skin, with the additional possibility of causing toxicity once absorbed systemically. Despite its potential toxicity, there are no reports on the in vivo bioavailability of hexamethylenetetramine following oral or dermal administration. In this study, we developed a new simple and sensitive LC-MS/MS method for the determination of hexamethylenetetramine in plasma and applied this method to characterize the toxicokinetics. The developed assay had a sufficient specificity and sensitivity for toxicokinetic characterization, and its accuracy and precision were verified. Following iv injection, the plasma concentration of hexamethylenetetramine showed mono exponential decay, with an elimination half-life of about 1.3 h. Following oral administration, the Tmax reached an average of 0.47 h and bioavailability was estimated as 89.93%. After percutaneous administration, it reached Cmax on average at 2.9-3.6 h. Although the absorption rate was relatively slow, its average bioavailability was calculated as 77.19-78.91%. Overall, most of the orally and percutaneously administered hexamethylenetetramine was absorbed into systemic circulation. The derived results in this study are expected to be utilized as the scientific evidence for further toxicokinetic study and risk assessment.

Chemopreventive Activity of Ellagitannins from Acer pseudosieboldianum (Pax) Komarov Leaves on Prostate Cancer Cells.

Several studies have shown that compounds from Acer pseudosieboldianum (Pax) Komarov leaves (APL) display potent anti-oxidative, anti-inflammatory, and anti-proliferative activities. Prostate cancer (PCa) is the most common cancer among older men, and DNA methylation is associated with PCa progression. This study aimed to investigate the chemopreventive activities of the compounds which were isolated from APL on prostate cancer cells and elucidate the mechanisms of these compounds in relation to DNA methylation. One novel ellagitannin [komaniin (14)] and thirteen other known compounds, including glucose derivatives [ethyl-ß-D-glucopyranose (3) and (4R)-p-menth-1-ene-7,8-diol 7-O-ß-D-glucopyranoside (4)], one phenylpropanoid [junipetrioloside A (5)], three phenolic acid derivatives [ellagic acid-4-ß-D-xylopyranoside (1), 4-O-galloyl-quinic acid (2), and gallic acid (8)], two flavonoids [quercetin (11) and kaempferol (12)], and five hydrolysable tannins [geraniin (6), punicafolin (7), granatin B (9), 1,2,3,4,6-penta-galloyl-ß-D-glucopyranoside (10), and mallotusinic acid (13)] were isolated from APL. The hydrolyzable tannins (6, 7, 9, 10, 13, and 14) showed potent anti-PCa proliferative and apoptosis-promoting activities. Among the compounds, the ellagitannins in the dehydrohexahydroxydiphenoyl (DHHDP) group (6, 9, 13, and 14), the novel compound 14 showed the most potent inhibitory activity on DNA methyltransferase (DNMT1, 3a and 3b) and glutathione S-transferase P1 methyl removing and re-expression activities. Thus, our results suggested that the ellagitannins (6, 9, 13, and 14) isolated from APL could be a promising treatment option for PCa.

Simultaneous attenuation of hyperglycemic memory-induced retinal, pulmonary, and glomerular dysfunctions by proinsulin C-peptide in diabetes.

BACKGROUND: Hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic complications. Although coincident diabetic complications are reported, research on their development and treatment is limited. Thus, we investigated whether C-peptide can simultaneously inhibit HGM-induced retinal, pulmonary, and glomerular dysfunctions in diabetic mice supplemented with insulin. METHODS: Insulin-treated diabetic mice were supplemented with human C-peptide by subcutaneous implantation of K9-C-peptide depots for 4 weeks, and reactive oxygen species (ROS) generation, transglutaminase (TGase) activity, and vascular leakage were examined in the retina, lung, and kidney. RESULTS: We found hyperglycemia-induced persistent ROS generation and TGase activation after blood glucose normalization in the retina, lung, and kidney of insulin-supplemented diabetic mice. These pathological events were inhibited by systemic supplementation of human C-peptide via subcutaneous implantation of a thermosensitive biopolymer-conjugated C-peptide depot. ROS generation and TGase activation were in a vicious cycle after glucose normalization, and C-peptide suppressed the vicious cycle and subsequent endothelial permeability in human retinal endothelial cells. Moreover, C-peptide supplementation ameliorated HGM-induced retinal vascular leakage and neurodegeneration, pulmonary vascular leakage and fibrosis, and glomerular adherens junction disruption and vascular leakage. CONCLUSIONS: Overall, our findings demonstrate that C-peptide supplementation simultaneously attenuates vascular and neuronal dysfunctions in the retina, lung, and glomerulus of insulin-supplemented diabetic mice.

Graphene e-tattoos for unobstructive ambulatory electrodermal activity sensing on the palm enabled by heterogeneous serpentine ribbons.

Electrodermal activity (EDA) is a popular index of mental stress. State-of-the-art EDA sensors suffer from obstructiveness on the palm or low signal fidelity off the palm. Our previous invention of sub-micron-thin imperceptible graphene e-tattoos (GET) is ideal for unobstructive EDA sensing on the palm. However, robust electrical connection between ultrathin devices and rigid circuit boards is a long missing component for ambulatory use. To minimize the well-known strain concentration at their interfaces, we propose heterogeneous serpentine ribbons (HSPR), which refer to a GET serpentine partially overlapping with a gold serpentine without added adhesive. A fifty-fold strain reduction in HSPR vs. heterogeneous straight ribbons (HSTR) has been discovered and understood. The combination of HSPR and a soft interlayer between the GET and an EDA wristband enabled ambulatory EDA monitoring on the palm in free-living conditions. A newly developed EDA event selection policy leveraging unbiased selection of phasic events validated our GET EDA sensor against gold standards.

Association of diet quality score with the risk of mild cognitive impairment in the elderly.

BACKGROUND/OBJECTIVES: Although adherence to a higher diet quality may help prevent cognitive decline in older adults, literature for this in a Korean population is limited. Thus, the aim of this study was to examine the association between diet quality indices and the risk of mild cognitive impairment (MCI) in Korean older adults. SUBJECTS/METHODS: This cross-sectional study included 806 community-dwelling people aged 60 yrs and over in Korea. Diet quality was assessed via the revised Recommended Food Score (RFS) and alternate Mediterranean Diet Score (aMDS). Cognitive function was measured using a Korean version of the Mini-Mental State Examination (MMSE-KC). Associations between diet quality indices and MMSE-KC score were assessed with a general linear model after adjusting for covariates. Logistic regression was used to determine the association between diet quality indices and the risk of MCI. RESULTS: The prevalence of MCI was 35.3%. There were no significant trends between MMSE-KC scores and RFS and aMDS after adjusting for age, gender, education, exercise, living status, social activity, and alcohol drinking. Among total subjects, RFS was inversely associated with the risk of MCI after adjusting for covariates (Q5 vs. Q1; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.83). Among total subjects and men, aMDS was inversely related to the risk of MCI after adjusting for covariates (Q5 vs. Q1; OR, 0.51; 95% CI, 0.29-0.89 for total subjects; Q5 vs. Q1; OR, 0.36; 95% CI, 0.15-0.83 for men). CONCLUSIONS: Our results demonstrate that high diet quality evaluated by RFS and aMDS is inversely associated with the risk of MCI. Thus, high quality diet may reduce or retard cognitive decline in the old population. Longitudinal studies are needed to determine the causal relationship between diet quality and the risk of MCI in the elderly.

A fabric-based multifunctional sensor for the early detection of skin decubitus ulcers.

Monitoring biosignals at the skin interface is necessary to suppress the potential for decubitus ulcers in immobile patients confined to bed. We develop conformally contacted, disposable, and breathable fabric-based electronic devices to detect skin impedance, applied pressure, and temperature, simultaneously. Based on the experimental evaluation of the multifunctional sensors, a combination of robust AgNW electrodes, soft ionogel capacitive pressure sensor, and resistive temperature sensor on fabric provides alarmed the initiation of early-stage decubitus ulcers without signal distortion under the external stimulus. For clinical verification, an animal model is established with a pair of magnets to mimic a human decubitus ulcers model in murine in vivo. The evidence of pressure-induced ischemic injury is confirmed with the naked eye and histological and molecular biomarker analyses. Our multifunctional integrated sensor detects the critical time for early-stage decubitus ulcer, establishing a robust correlation with the biophysical parameters of skin ischemia and integrity, including temperature and impedance.

C-peptide attenuates hyperglycemia-induced pulmonary fibrosis by inhibiting transglutaminase 2.

Proinsulin C-peptide has a protective effect against diabetic complications; however, its role in hyperglycemia-induced pulmonary fibrosis is unknown. In this study, we investigated the inhibitory effect of C-peptide on hyperglycemia-induced pulmonary fibrosis and the molecular mechanism of C-peptide action in the lungs of diabetic mice and in human pulmonary microvascular endothelial cells (HPMVECs). We found that, in the lungs of diabetic mice, C-peptide supplementation using osmotic pumps attenuated hyperglycemia-induced pulmonary fibrosis and expression of fibrosis-related proteins. In HPMVECs, C-peptide inhibited vascular endothelial growth factor-induced adherens junction disruption and endothelial cell permeability by inhibiting reactive oxygen species generation and transglutaminase (TGase) activation. In the lungs, C-peptide supplementation suppressed hyperglycemia-induced reactive oxygen species generation, TGase activation, and microvascular leakage. C-peptide inhibited hyperglycemia-induced inflammation and apoptosis, which are involved in the pathological process of pulmonary fibrosis. We also demonstrated the role of TGase2 in hyperglycemia-induced vascular leakage, inflammation, apoptosis, and pulmonary fibrosis in the lungs of diabetic TGase2-null (Tgm2-/-) mice. Furthermore, we demonstrated a long-term inhibitory effect of systemic delivery of C-peptide using K9-C-peptide hydrogels on hyperglycemia-induced fibrosis in diabetic lungs. Overall, our findings suggest that C-peptide alleviates hyperglycemia-induced pulmonary fibrosis by inhibiting TGase2-mediated microvascular leakage, inflammation, and apoptosis in diabetes.

Midazolam Ameliorates Hyperglycemia-Induced Glomerular Endothelial Dysfunction by Inhibiting Transglutaminase 2 in Diabetes.

Midazolam is an anesthetic widely used for anxiolysis and sedation; however, to date, a possible role for midazolam in diabetic kidney disease remains unknown. Here, we investigated the effect of midazolam on hyperglycemia-induced glomerular endothelial dysfunction and elucidated its mechanism of action in kidneys of diabetic mice and human glomerular microvascular endothelial cells (HGECs). We found that, in diabetic mice, subcutaneous midazolam treatment for 6 weeks attenuated hyperglycemia-induced elevation in urine albumin/creatinine ratios. It also ameliorated hyperglycemia-induced adherens junction disruption and subsequent microvascular leakage in glomeruli of diabetic mice. In HGECs, midazolam suppressed high glucose-induced vascular endothelial-cadherin disruption and endothelial cell permeability via inhibition of intracellular Ca2+ elevation and subsequent generation of reactive oxygen species (ROS) and transglutaminase 2 (TGase2) activation. Notably, midazolam also suppressed hyperglycemia-induced ROS generation and TGase2 activation in glomeruli of diabetic mice and markedly improved pathological alterations in glomerular ultrastructure in these animals. Analysis of kidneys from diabetic Tgm2-/- mice further revealed that TGase2 played a critical role in microvascular leakage. Overall, our findings indicate that midazolam ameliorates hyperglycemia-induced glomerular endothelial dysfunction by inhibiting ROS-mediated activation of TGase2.

Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers.

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1ß), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-ß, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.

Anti-aging effect of an oral disintegrating collagen film: a prospective, single-arm study.

BACKGROUND: As the average life expectancy increases, skin aging and wrinkles due to photoaging have gained attention. Collagen is closely involved in the process of skin aging. Among the potential methods of drug delivery to the skin, oral disintegrating films show promise for their ability to bypass the loss of active components that is typical of drug absorption via oral administration. This study was conducted to investigate the effect of an oral disintegrating collagen film on skin aging. METHODS: We performed a prospective, single-arm study in a cohort of 22 women to assess the anti-aging effect of a novel oral disintegrating film containing collagen applied daily over a 12-week period. We measured the clinical indicators of skin integrity and performed immunofluorescence and high-performance liquid chromatography analyses of an ex vivo oral mucosa model to compare the absorption rates of collagen films and conventional oral tablets via the mucosa. RESULTS: We found that the oral disintegrating collagen film reduced skin wrinkle depth and number and significantly increased skin elasticity and density. CONCLUSIONS: The novel mode of delivery of collagen via oral disintegrating films has a clinically potential anti-aging efficacy and is safe and convenient for daily use.

Synergistic Effect of 300 µm Needle-Depth Fractional Microneedling Radiofrequency on the Treatment of Senescence-Induced Aging Hyperpigmentation of the Skin.

Aging-associated dermatological pigmentary diseases are associated with accumulation of senescence cells and the disruption of basement membrane due to chronic ultraviolet radiation (UVR) exposure. Our study is on the synergistic effect of the novel 300 µm needle-depth fractional microneedling radiofrequency (FMR) treatment and conventional Q-switched ND:YAG laser on aging-associated hyperpigmentation of the skin. The prospective controlled clinical trial of 25 Asian women revealed significantly higher improvements not only on wrinkles, but also on hyperpigmentation. Additional ex vivo study revealed significant reduction of pro-melanogenic markers as well as senescent keratinocytes, while increased expression of collagen type IV on the epidermal basement membrane, after additional FMR treatment on UV-irradiated human tissues. These results demonstrate that 300 µm needle-depth FMR might effectively remove senescent keratinocytes that secrete pro-melanogenic markers, and repair disrupted basement membrane, therefore preventing constant hyperpigmentation of the aged skin.

Interaction of genetic and environmental factors for body fat mass control: observational study for lifestyle modification and genotyping.

Previous studies suggested that genetic, environmental factors and their interactions could affect body fat mass (BFM). However, studies describing these effects were performed at a single time point in a population. In this study, we investigated the interaction between genetic and environmental factors in affecting BFM and implicate the healthcare utilization of lifestyle modifications from a personalized and genomic perspective. We examined how nutritional intake or physical activity changes in the individuals affect BFM concerning the genetic composition. We conducted an observational study including 259 adult participants with single nucleotide polymorphism (SNP) genotyping and longitudinal lifestyle monitoring, including food consumption and physical activities, by following lifestyle modification guidance. The participants' lifelog data on exercise and diet were collected through a wearable device for 3 months. Moreover, we measured anthropometric and serologic markers to monitor their potential changes through lifestyle modification. We examined the influence of genetic composition on body fat reduction induced by lifestyle changes using genetic risk scores (GRSs) of three phenotypes: GRS-carbohydrate (GRS-C), GRS-fat (GRS-F), and GRS-exercise (GRS-E). Our results showed that lifestyle modifications affected BFM more significantly in the high GRS class compared to the low GRS class, indicating the role of genetic factors affecting the efficiency of the lifestyle modification-induced BFM changes. Interestingly, the influence of exercise modification in the low GRS class with active lifestyle change was lower than that in the high GRS class with inactive lifestyle change (P = 0.022), suggesting the implication of genetic factors for efficient body fat control.

Transcriptome Analysis Reveals That Abeliophyllum distichum Nakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly Through Suppressing Nfatc1 Expression.

Abeliophyllum distichum Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that A. distichum extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of A. distichum extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of A. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract of A. distichum efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.

Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus.

Platycodon grandiflorus (Jacq.) A.DC. (PG) has long been used as an ingredient of foods and is known to have beneficial effects on cognitive functions as well. The present study examined the effect of each PG extract (PGE) from root, aerial part, and seeds on cognitive functions in mice. Changes in spatial learning and memory using a Y-maze test, and markers of adult hippocampal neurogenesis and synaptogenesis were examined. Moreover, changes in neuritogenesis and activation of the ERK1/2 pathway were investigated. Results indicated that mice administered PGE (root) showed increased spontaneous alternation in the Y-maze test and synaptogenesis in the hippocampus. In addition, PGE (root) and platycodin D, the major bioactive compound from the PG root, significantly stimulated neuritic outgrowth by phosphorylation of the ERK1/2 signaling pathway in vitro. These results indicate that the PGE (root), containing platycodin D, enhances cognitive function through synaptogenesis via activation of the ERK1/2 signaling pathway.